tbuckley/cabot-search huggingface dataset:
Time to response, duration of response, and patient-reported outcomes (PROs) with daratumumab (DARA) plus lenalidomide and dexamethasone (D-Rd) versus lenalidomide and dexamethasone (Rd) alone in transplant-ineligible patients with newly diagnosed multiple myeloma (NDMM): Subgroup analysis of the phase 3 MAIA study.
Authors: Thierry Facon, Shaji Kumar, Torben Plesner, Philippe Moreau, Nizar J. Bahlis, Hartmut Goldschmidt, Michael O'Dwyer, Aurore Perrot, Christopher P. Venner, Katja Weisel, Joseph R. Mace, Noopur S. Raje, Mourad Tiab, Margaret Macro, Laurent Frenzel, Xavier Leleu, Huiling Pei, Fredrik Borgsten, Saad Zafar Usmani
Journal: Journal of Clinical Oncology (2022)

8044 Background: In the phase 3 MAIA study, adding DARA to Rd improved progression-free survival (primary endpoint), overall survival, duration of response, and PROs in transplant-ineligible pts with NDMM. We report a MAIA subgroup analysis of time to response, duration of response, and PROs. Methods: Transplant-ineligible pts with NDMM received 28-day cycles of Rd (R 25 mg PO on Days 1-21; d 40 mg PO QW) ± DARA (16 mg/kg IV QW in Cycles 1-2, Q2W in Cycles 3-6, and Q4W thereafter) until disease progression or unacceptable toxicity. Secondary endpoints included time to response and duration of response. PROs were measured using the EORTC QLQ-C30, with treatment effects assessed via mixed-effects model with repeated measures. Results: In total, 368 pts were assigned to the D-Rd group and 369 pts to the Rd group; 162 (44%) D-Rd pts and 142 (38%) Rd pts had renal impairment (defined as baseline CrCl ≤60 mL/min). At a 56.2-mo median follow-up, median times to very good partial response or better (≥VGPR) and complete response or better (≥CR) were shorter with D-Rd vs Rd in the overall study population and in the subgroups of pts with and without renal impairment (Table). Among pts who achieved ≥CR or partial response or better (≥PR), higher proportions of D-Rd vs Rd pts had not experienced disease progression at 48 mo (Table). Among pts with renal impairment, greater improvements from baseline in pt-reported pain, fatigue, and nausea and vomiting symptom scores were observed with D-Rd vs Rd across most timepoints; a notably greater meaningful reduction in pain symptom score was seen with D-Rd vs Rd as early as Cycle 6 Day 1 (least squares mean change from baseline, −14.9 vs −7.0; P=0.0241). Analyses for additional pt subgroups will be presented. Conclusions: In transplant-ineligible pts with NDMM, D-Rd showed more rapid deep responses as well as more durable responses vs Rd, regardless of renal function. Improvements in pt-reported symptoms were generally greater with D-Rd vs Rd in pts with renal impairment. Our results support the use of D-Rd in transplant-ineligible pts with NDMM. Clinical trial information: NCT02252172. [Table: see text]
Utility of Anorectal Testing to Predict Outcomes With Pelvic Floor Physical Therapy in Chronic Constipation: Pragmatic Trial
Authors: Eric D Shah, Elizabeth A Pelletier, Carol Greeley, Emily E Sieglinger, Jamie D Sanchez, Kayla A Northam, Jessica A Perrone, Michael A Curley, Christopher M Navas, Tracy L Ostler, Aimee R Burnett Greeley, Pablo Martinez-Camblor, Jason R Baker, William D Chey
Journal: Clinical Gastroenterology and Hepatology (2022)
Sociodemographic trends in COVID-19 mortality in patients with cancer: A nationwide analysis.
Authors: Sree Jambunathan, Jacob Lang, Malik Mays, Mersiha Hadziahmetovic, Oluchi Ukaegbu Oke, Obi Ekwenna
Journal: Journal of Clinical Oncology (2022)

10571 Background: The COVID-19 pandemic has caused unprecedented disruptions in medical care, especially in those with cancer. Prior studies have demonstrated a higher risk of mortality in patients with cancer and COVID-19, which could be due to factors such as immunosuppression and higher burden of co-morbidities. However, there are limited studies examining the impact of sociodemographic factors including race, gender, rurality, and region on mortality in patients with COVID-19 and cancer. This study aims to characterize and analyze sociodemographic trends in COVID-19 mortality in patients with cancer. Methods: Data on patients with COVID-19 and cancer listed on death certificates from the Multiple Cause of Death Centers for Disease Control and Prevention Wide-Ranging Online Data for Epidemiologic Research (CDC WONDER) database were extracted. Age-adjusted mortality rates (AAMR) were calculated and compared across sociodemographic groups. Results: A total of 18,467 total deaths occurred in patients with COVID-19 and cancer listed on multiple cause of death certificates in 2020, with overall AAMR of 4.4 (95% CI: 4.4-4.5). AAMR for patients with COVID-19 and cancer was significantly higher in Non-Hispanic (NH) Black or African American (7, 95% CI: 6.8-7.3), NH American Indian or Alaska Native (6.4, 95% CI: 5.4-7.3), and Hispanic or Latino (5.4, 95% CI: 5.2-5.7) groups than NH White (4, 95% CI: 3.9-4.1) and NH Asian or Pacific Islander (2.5, 95% CI: 2.3-2.7). AAMR was also higher in males (5.9, 95% CI: 5.8-6.1) and those in Northeast (5.6, 95% CI: 5.4-5.8) and Midwest (5.3, 95% CI: 5.2-5.5) census regions. Those in medium metro counties had significantly lower AAMR (3.8, 95% CI: 3.7-4) compared to other locations based on the NCHS Urban-Rural Classification Scheme for Counties. Conclusions: AAMR in patients with any cancer and COVID-19 was significantly higher in NH Black or African American, NH American Indian or Alaskan, and Hispanic or Latino race/ethnicity groups, as well as in males. Regional and rurality disparities also exist. This study highlights persistent disparities in COVID-19 and cancer outcomes and identifies groups at higher risk of mortality. Future studies examining sociodemographic trends in COVID-19 mortality in patients with specific cancers are necessary. [Table: see text]
The effects of vascular endothelial cells on regulating post-irradiation microglia phenotype in irradiation-induced brain injury.
Authors: Jiaojiao Wang, Fan Tong, Zhenyu Lin, Xiaorong Dong
Journal: Journal of Clinical Oncology (2022)

e14001 Background: The purpose was to elucidate the mechanism behind functional relevance between microglia and injured blood vessels after CRT and the role of fractalkine (FKN) for the dynamics in the microglia phenotype, hoping to provide a theoretical rationale for the therapeutic strategy of Radiation-induced brain injury (RIBI). Methods: The ultrastructural blood vessels in the hippocampus were examined by transmission electron microscopy. EMSA and dual-luciferase assays were used to confirm the activation of NF-κB induced by irradiation in. Migration and co-culture assays were used to investigate the the association between HUVEC and BV-2 cells after irradiation. We constructed CX3CR1-knockdown (receptor of FKN) lentiviral vector to produce CX3CR1-knockdown BV-2 cell lines. After cultured for 3h with/without FKN, BV-2 cells (Sh-NC/ Sh-CX3CR1) received 10-Gy irradiation. The CX3CR1wide-type/knockdownmice were used and subjected to lateral ventricular injection (ICV) of 5 μl FKN lentivirus or vector before CRT. The in vitro and in vivo phenotype transformation of microglia and its inflammatory factors release were detected by WB, real-time PCR, ELISA, and IF at different time-points after irradiation. Morris water maze test was used to test mice's cognitive function. Results: In the hippocampus of the CRT group, significant pathological changes were seen in ultrastructure of blood vessels.The NF-κB pathway was activated in vascular endothelial cells (ECs) after10-Gy irradiation. In vitro migration and Co-culture assays found that molecular signals, secreted by ECs via the NF-κB pathway, leading to the activation of microglia and their recruitment to blood vessels. ELISA and qRT-PCR revealed that 10-Gy irradiation promoted the secretion of FKN from the vascular ECs via activating the NF-κB pathway. Western blotting and Flow cytometry showed that pretreatment with exogenous FKN, before 10-Gy irradiation, promoted microglia M2 phenotype transformation, diminished radiation-induced pro-inflammatory factors, and enhanced phagocytosis capacity. In addition, in vivo experiments showed that up-regulation of FKN via FKN lentivirus promoted radiation-induced microglial M2 transformation in the hippocampus, and diminished the spatial memory injury of radiated mice. Lastly, while inhibiting the CX3CR1, which is exclusively expressed on microglia in the brain, the regulatory effect of FKN on microglia and cognitive ability of mice disappeared after radiation. Conclusions: FKN, mainly secreted by vascular ECs via the NF-κB pathway after radiation, may attenuate RIBI through microglia polarization toward M2 phenotype by binding to CX3CR1 on microglia. Our study has unveiled an important and novel role of FKN/CX3CR1 in RIBI, providing evidence to validate that promotion of the FKN/CX3CR1 axis could be a promising therapeutic strategy for the treatment of RIBI.
Variability in diagnostic performance of non-muscle invasive bladder cancer for each region using fluorescence cystoscopy with orally administered 5-aminolevulinic acid
Authors: Y. Ishikawa, S. Uehara, K. Ishihara, K. Hirose, T. Soma, M. Fujiwara, M. Kobayashi, B. Fan, Y. Nakamura, Y. Uchida, S. Fukuda, H. Tanaka, S. Yoshida, M. Yokoyama, Y. Matsuoka, Y. Fujii
Journal: European Urology (2022)
Impact of pretreatment clinical factors and DVH parameters on radiation pneumonitis and survival after intensity-modulated radiotherapy for lung cancer.
Authors: ZiBin Liang, Xiaolu Xu, Shuanshuan Guo, Xiaoli Niu, Lubin Yan, Yanfei Zou, Zhong Lin, Peijian Peng, Zhihui Wang, Liyang Hu
Journal: Journal of Clinical Oncology (2022)

e20571 Background: The aim of this study was to investigate the relationship between clinical factors and dose-volume histogram parameters regarding Overall Survival (OS) and Radiation-Pneumonitis-Free Survival (RPFS) in lung cancer patients. Methods: We retrospectively reviewed clinical data of lung cancer patients from 2018 to 2020. Demographic, clinical, and treatment-related data were collected for all patients. OS was defined as the duration from pathological diagnosis to death or last follow-up. RPFS was defined as the duration from the start of radiation therapy to occurrence of grade≥3 Radiation-Pneumonitis, or final follow-up. RPFS and OS rates were estimated with the Kaplan-Meier method and compared using the log-rank test. The Cox regression model was used to estimate the hazard ratio (HR) and the corresponding 95% confidence interval (CI) for univariate and multivariate analysis. Results: A-hundred patients were included in this study. The median follow-up period after completion of radiotherapy was 42.9months (range: 2.0–152.1). In multivariate study, low serum sodium after RT, V5ipsi≥51%, V20ipsi≥28%, V30ipsi≥22% and MLDipsi≥15.99 Gy were independent predictive factors for poor OS, respectively ( p ＜0.05). MLD≥10.20 Gy suggested a poorer RPFS ( p ＜0.1) in this cohort. Conclusions: The independent significant risk factors of radiation pneumonitis were V20, V5 and MLD. In addition, the V20 and V5 of the ipsilateral lung should be more strictly limited to less than 28% and 51% when determining radiotherapy especially in this era of immunotherapy. Some blood indexes of low nutritional status were very important to determine the occurrence of high-risk radiation pneumonitis.
Survival and prognostic factors in oligometastatic breast cancer.
Authors: Annemiek Van Ommen - Nijhof, Tessa Gerjanne Steenbruggen, Laura C. Capel, Michel J.P. Vergouwen, Marie-Jeanne T.F.D Vrancken Peeters, Terry G. Wiersma, Gabe S. Sonke
Journal: Journal of Clinical Oncology (2022)

1089 Background: Clinical guidelines for the treatment of oligometastatic breast cancer (OMBC) propagate multimodality treatment including polychemotherapy and ablative local therapy for all detected disease. The aim of this aggressive approach is prolonged disease remission, or even cure, but randomized data to support this strategy lack and long-term outcomes are not well known. We report prognostic factors, and event-free survival (EFS) and overall survival (OS) in a real world, single center cohort of patients with OMBC with long-term follow-up. Methods: Patients with breast cancer and 1-3 distant metastatic lesions who underwent treatment in the Netherlands Cancer Institute were identified via text mining of medical files. We collected patient, tumor and treatment characteristics as well as recurrence and survival data from the medical records. The Kaplan-Meier method was used to calculate EFS and OS estimates, and Cox regression analyses to assess potential prognostic factors. Results: The cohort included 239 patients (of whom two males), diagnosed between 1997 and 2020. Median follow-up was 75.0 months. Fifty-one percent had hormone receptor (HR)-positive/ human epidermal growth factor receptor 2 (HER2)-negative disease, 20.1% had HER2-positive disease, and 19.2% had triple negative (TN) disease. Median age at OMBC diagnosis was 49.0 years and 47.3% of patients had synchronous disease (metastases ≤6 months of primary diagnosis). Most patients (81.2%) received chemotherapy and local therapy (surgery, radiotherapy and/or radiofrequency ablation) of all metastatic lesions (83.7%). Of 239 patients, 134 experienced disease recurrence with a median EFS of 40.0 months (95% confidence interval (CI): 28.6-51.4); 97/239 died and median OS was 93.0 months (95% CI 74.5-111.5). The table shows factors associated with favorable OS in multivariable analysis. Cox regression analysis for EFS showed similar results. Conclusions: In this large real world cohort of OMBC patients, EFS and OS compare favorably to survival in the general MBC population. HR-positive and/or HER2-positive subtypes, synchronous disease or long DFI, favorable response to first-line systemic therapy and local therapy of all distant lesions are independently associated with better survival. Future studies should be directed at optimizing patient selection and therapy choices in this population with the potential for cure. [Table: see text]
MODL-07. DNA methylation-based biobank of murine models for pediatric tumors
Authors: Tuyu Zheng, Martin Sill, Roland Imle, Ryo Shiraishi, Wanchen Wang, Alaide Morcavallo, Louis Chesler, Daisuke Kawauchi, Olivier Ayrault, Lutsik Pavlo, Stefan M Pfister, Lena M Kutscher, Ana Banito, David W Jones, Kristian W Pajtler, Marc Zuckermann
Journal: Neuro-Oncology (2022)

Abstract Recent advances in molecular profiling methods led to the identification of multiple new molecularly defined tumor types and subtypes, distinguished by distinct molecular markers and characteristic DNA methylation signatures. While the analysis of human methylome using microarrays has become an affordable and a routine in many labs, this technology until recently was not available for murine samples. In the past years, we have successfully generated a variety of mouse models for childhood tumors (e.g brain tumors and sarcomas) using different techniques, most of which faithfully reflect the human tumor counterparts at the histological level. With the recently released Infinium Mouse Methylation BeadChip, we now set out to use our models to generate the first DNA methylation database for murine pediatric tumors. We profiled more than 70 mouse models of pediatric tumors including gliomas, medulloblastomas, ependymomas and sarcomas, as well as 40 normal brain and muscle control tissues. We are currently performing a cross-species comparative analysis of established mouse models and the human counterparts. This will assess, how faithfully each models reflect the human situation and examine the effects of multiple passages of allografting. We will also analyze purified immune cell populations and use the derived methylation signatures to assess the model-specific immune microenvironment. Furthermore, we will investigate the methylomes of multiple putative cells-of-origin, which is hardly possible in the human context due to the lack of purified material. We will correlate these to murine tumor samples and thereby provide novel insights into tumor origins. In summary, our study will generate a validated biobank of murine models for pediatric cancers and provide a valuable resource for future developmental studies and preclinical trials.
Association of time intervals in cancer screenings and older participants’ characteristics, in a U.S. nationally representative sample.
Authors: Marianne Razavi, Cristiane Decat Bergerot, Errol James Philip, William Dale
Journal: Journal of Clinical Oncology (2022)

e24020 Background: Various guidelines regarding cancer screening intervals for older adults exist. They often differ based on age cut-offs. There is limited national data about factors impacting adherence to these guideline-based intervals. Using a national-representative dataset, self-reported screening rates between men and women for breast (Mammogram) or prostate (PSA) cancer were explored. The demographic and lifestyle characteristics associated with screening time intervals were also investigated. Methods: Data from the nationally representative National Social Life Health and Aging Project Wave 3 (NSHAP-W3, 2015) was used. Individuals with no history of cancer were asked: How long has it been since you last had a screening (Mammogram or PSA). Responses ranged from 1 = within the past year, 2 = between one and five years ago , 3 = more than five but less than ten years ago, 4 = ten or more years ago, 5 = never. Age groups consisted of 50-54, 55-59, 60-64, 65-69, 70-74, 75-79, ≥80. Ordinal Logistic regression was used to study the association between screening time intervals (Mammogram or PSA) and participants’ characteristics (demographic, emotional, self-reported physical health, and physical activity). Results: Community-dwelling older adults (n = 2,320) were included (52% women, 48% men, with mean age of 66.9 years). There was a curvilinear response by age. The middle-age groups (60 thru 79) were significantly more likely to report shorter screening intervals, compared to the youngest group (50-54) and oldest group (≥80): ORs ranging from 0.30 to 0.61. No significant differences were observed between the oldest and youngest groups. Higher household income was associated with shorter time intervals (Mammogram: OR = 0.77; PSA: OR = 0.78, p &lt; 0.001). African Americans were more likely to report shorter intervals between Mammograms (OR = 0.43, p &lt; 0.001), compared to white women. More physically active men were likely to report shorter intervals (OR = 0.92, p = 0.021). Conclusions: Participants who are in their 60s or 70s, are more likely to have shorter time intervals between cancer screenings. African American women, and men performing frequent exercise are also more likely to have shorter intervals. These results emphasize the importance of sociodemographic and lifestyle factors, when seeking to impact cancer screening timing.
A phase II study of hyper-CVAD with sequential blinatumomab (Blina), with or without inotuzumab ozogamicin (INO), in adults with newly diagnosed B-cell acute lymphoblastic leukemia (ALL).
Authors: Nicholas James Short, Hagop M. Kantarjian, Farhad Ravandi, Musa Yilmaz, Tapan M. Kadia, Philip A. Thompson, Marina Konopleva, Alessandra Ferrajoli, Nitin Jain, Koji Sasaki, Yesid Alvarado Valero, Gautam Borthakur, Courtney Denton Dinardo, Maro Ohanian, Walid Macaron, Rebecca Garris, Min Zhao, Monica Kwari, Christopher Loiselle, Elias Jabbour
Journal: Journal of Clinical Oncology (2022)

7034 Background: Blina and INO are highly effective in relapsed/refractory B-cell ALL and are associated with high rates of measurable residual disease (MRD) clearance. Use of these agents in the frontline setting may improve outcomes. Methods: Patients (pts) 14-59 years of age with newly diagnosed Philadelphia chromosome (Ph)-negative B-cell ALL, including pts who had received no more than 1 prior cycle of chemotherapy, were eligible. Pts received hyper-CVAD alternating with high-dose MTX/Ara-C for up to 4 cycles, followed by 4 cycles of Blina. Pts with CD20+ disease received 8 doses of an anti-CD20 antibody. Eight doses of IT chemotherapy were given. Maintenance was with alternating blocks of POMP (maintenance cycles 1-3, 5-7, 9-11, and 13-15) and Blina (maintenance cycles 4, 8, and 12). Beginning with pt #39, INO at a dose of 0.3 mg/m2 on day 1 and 8 was added to the 2 cycles of MTX/Ara-C and to 2 cycles of Blina (4 total cycles with INO). Results: Characteristics of the 58 treated pts (38 without INO and 20 with INO) are summarized in Table. Among 45 pts with active disease at study entry, 100% achieved CR. Overall, 76% achieved MRD negativity by flow cytometry after induction and 95% at any time over the course of therapy. The median follow-up of the entire cohort is 26 months (range, 3-61+ months). Overall, 5 pts (9%) relapsed, 18 (31%) underwent transplant in first remission (including an additional 2 pts who relapsed post-transplant), 2 (3%) died in CR, and 33 (57%) remain in continuous remission without transplant. All relapses occurred in pts with established poor-risk features and no relapses have occurred beyond 2 years. For the entire cohort, the estimated 3-year OS is 85% and the 3-year continuous remission duration is 84%. No relapses or deaths have occurred in the INO group, and the estimated 1-year OS is 100%. Treatment was overall well-tolerated. One patient discontinued Blina due to recurrent grade 2 neurotoxicity. No pts have discontinued INO due to toxicity and no cases of veno-occlusive disease have been observed. Conclusions: Hyper-CVAD with sequential Blina is highly effective as frontline treatment of Ph-negative B-cell ALL. The addition of INO to this regimen was safe and early results are encouraging, with no relapses observed to date. Clinical trial information: NCT01371630. [Table: see text]
Helium conditioning increases cardiac fibroblast migration which effect is not propagated via soluble factors or extracellular vesicles
Authors: C Kovacshazi, M Jelemensky, K Ferenczyova, M Hofbauerova, B Kiss, E Pallinger, A Kittel, V N Sayour, A Gorbe, SZ Hambalko, L Kindernay, M Barancik, P Ferdinandy, M Bartekova, Z Giricz
Journal: Cardiovascular Research (2022)

Abstract Funding Acknowledgements Type of funding sources: Public grant(s) – National budget only. Main funding source(s): Project was supported by the National Research, Development and Innovation Office of Hungary Background Helium inhalation induces cardioprotection against ischemia/reperfusion injury, of which cellular mechanism is not fully elucidated. Extracellular vesicles (EVs) are cell-derived, nano-sized membrane vesicles which play role in cardioprotective mechanisms, but their function in helium-conditioning (HeC) is not elucidated. Purpose To investigate, how HeC affects cardiac fibroblasts and if their HeC-induced EVs or other secreted factors mediates remodeling of the cardiac tissue. Methods Neonatal rat cardiac fibroblasts (NRCF) were exposed to glucose deprivation and HeC rendered by four cycles of 95% helium + 5% CO2 for one hour, followed by one hour of normal culturing conditions. 40 hours later, NRCF migration was analyzed and Western Blot and quantitative PCR were used to analyze the expression of fibroblast to myofibroblast transformation markers. From the cell supernatant, medium-sized extracellular vesicles (mEVs) were isolated with differential centrifugation and analyzed with WB, transmission electron microscopy and nanoparticle tracking analysis. Supernatant of HeC-treated NRCF was transferred to naïve NRCF or immortalized human umbilical vein endothelia cells (HUVEC/TERT2) and migration and in vitro angiogenesis assay was performed. Results HeC accelerated the migration of NRCF. Meanwhile, HeC did not increase the expression of myofibroblast markers. HeC tended to decrease mEV secretion of NRCFs, but supernatant of HeC-NRCF neither accelerate the migration of naïve NRCF, nor affect the angiogenic potential of HUVEC/TERT2. Conclusion Since HeC increased the migration of NRCF but HeC-NRCF mEVs did not affect the function of remote cells, HeC may exert its cardioprotective effect via NRCFs, but not affect cardiac remodeling remotely, via NRCF mEVs.